Millions of people are exposed to arsenic-contaminated water in the U.S. and worldwide, and arsenic is[unreadable] ranked first on the most recent priority list of Superfund site hazardous substances. Current evidence[unreadable] suggests that lung cancer is the leading cause of arsenic-associated mortality. In addition, arsenic also[unreadable] increases the incidence of non-malignant pulmonary disease, and intriguing preliminary evidence obtained[unreadable] by our research group suggests that those exposed as young children or in utero are particularly[unreadable] susceptible to both the malignant and non-malignant pulmonary effects of arsenic. We propose a series of[unreadable] investigations to further explore the effects of childhood arsenic exposure and the mechanisms that may[unreadable] confer susceptibility to these effects. The proposed epidemiological studies include a case-control study of[unreadable] childhood and in utero arsenic exposure and subsequent risks of lung cancer in young adults in Northern[unreadable] Chile, and a cross-sectional study of lung function and respiratory health and arsenic exposure involving[unreadable] children in West Bengal. In addition, biological samples collected during these studies, combined with[unreadable] samples collected from several of our past studies, will be used for additional investigations on arsenic[unreadable] susceptibility and mechanisms of toxicity including: 1). Susceptibility related to individual differences in[unreadable] urinary concentrations of MMA3, a highly toxic but rarely studied arsenic metabolite; 2). Susceptibility[unreadable] related to genetic polymorphisms, in particular those involving AS3MT (cyt19), GSTO1, GSTM1, and[unreadable] EGFR. 3). Assessment of urinary proteomic patterns as biomarkers of exposure, disease, and[unreadable] susceptibility. In past years, Superfund has provided the core funding that has allowed us to make many[unreadable] new and important contributions to research on arsenic. Our goal is to continue this successful model, but[unreadable] with a new focus on the respiratory effects of childhood and in utero exposures and the associated[unreadable] mechanisms of toxicity and susceptibility. Given the widespread exposure to ingested arsenic in the U.S.[unreadable] and worldwide, and the very high risks of lung disease following early life exposures we have seen in our[unreadable] preliminary studies, investigating these effects has the potential to yield important new public health and[unreadable] scientific information regarding the in utero and childhood effects of toxic substances.